Is CHRNE p.Phe310fs (c.929del) pathogenic?

CHRNE p.Phe310fs (c.929del) is classified Likely pathogenic in CHRNE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-28). Very rare (popmax 8.56e-05%, nfe); Associated with congenital myasthenic syndrome 4A.

What condition is associated with CHRNE p.Phe310fs (c.929del)?

CHRNE p.Phe310fs (c.929del) is associated with congenital myasthenic syndrome 4A (ClinVar).

How common is CHRNE p.Phe310fs (c.929del) in the general population?

CHRNE p.Phe310fs (c.929del) is very rare (popmax 8.56e-05%, nfe) (gnomAD).

CHRNE p.Phe310fs

c.929del · rs2507544168 · VCV2680782

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.56e-05%, nfe)

Conditions

congenital myasthenic syndrome 4A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.9	GERP 0.96, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.56e-05% European (non-Finnish) · 1/1,167,544 alleles

Overall 6.97e-05% 1/1,434,966 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CHRNE
Protein: p.Phe310fs
Coding: c.929del
MANE Select: NM_001145536 · reported on NM_000080
dbSNP: rs2507544168
Type: Deletion
Location: chr17:4899571 (GRCh38)

Full CHRNE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myasthenic syndrome 4A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/chrne-p-phe310fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown